This content is current only at the time of printing. This document was printed on 15 October 2019. A current copy is located at https://apvma.gov.au/node/31421
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Worker health and safety risk assessments undertaken by the APVMA
The Australian Pesticide and Veterinary Medicines Authority has reconsidered its almost exclusive use of route-to-route extrapolation for its worker health and safety (WHS) risk assessments. Occupational exposure arising from mixing/loading or spraying pesticides comes primarily through skin contact and/or by inhalation. The first consideration for a WHS risk assessment is to identify all toxicological hazards in studies where the treatment conditions in experimental animals are similar to the route of human professional exposure (ie. dermal and inhalational, five days per week and six hours per day).
Most toxicological databases for pesticides submitted to regulatory agencies include a 21 or 28 day (or in some cases thirteen weeks) rat or rabbit dermal toxicity study. In the absence of such studies, a route-to-route extrapolation using a dietary repeat-dose oral toxicity study will need to be considered. If a gavage or dietary administration study is used for the WHS assessment then a dermal absorption factor will also need to be identified.
In most cases, a detailed dermal exposure risk assessment will not be necessary if no systemic toxicity was observed in the repeat-dose dermal toxicity study at a limit dose of 1000 mg/kg bw/day. Portal-of-entry effects in such studies, eg. dermal irritation, can be considered in conjunction with the acute toxicity effects of the product formulation. If systemic toxicity observed in oral dosing studies indicates adverse effects that were not tested in the dermal study (eg. developmental or neuropathology), then a dermal developmental study or a suitable oral dosing study for route-to-route extrapolation should be used. Another important consideration is whether steady-state (ie. plasma concentration is in equilibrium with its elimination) has been achieved. If the pharmacokinetic data in laboratory animals suggests that plasma steady-state concentrations have not been achieved within the duration of the dermal study then dermal toxicity data is not recommended. In such cases a suitable duration oral dosing study will need to be selected for a route-to-route extrapolation.
For most pesticides, dermal exposure is the most important consideration for determining occupational risk. However, for certain volatile pesticides such as fumigants or when used in confined spaces, eg. for pest controllers it is necessary to consider the inhalational risk. In such situations, it is appropriate to use short-term inhalational studies as the comparator to derive margins of exposure (MOE). MOE = NOAEL/exposure expressed in mg/kg bw/day. In such situations, it is necessary to convert the repeat dose inhalational exposure expressed in mg/m3 (or mg/L) in the laboratory animal study to an equivalent oral dose (expressed as mg/kg bw/day).
For most pesticide application scenarios specific exposure data (eg. Mixer/Loader and Applicators) are not available. In such situations the APVMA will routinely determine the dermal and inhalational exposure using the Pesticide Handlers Exposure Database (PHED); United States Environmental Protection Agency (US EPA). For pesticides whose vapour pressure is greater than 1 x 10-3 mm Hg (0.13 Pa), eg. fumigants, PHED is not suitable. For such compounds, a Probabilistic Exposure And Risk Model For Fumigants (US EPA) will be considered.